A randomized clinical trial comparing ritonavir-boosted lopinavir versus raltegravir each with tenofovir plus emtricitabine for post-exposure prophylaxis for HIV infection.

OBJECTIVES: The objective of this study was to assess post-exposure prophylaxis (PEP) non-completion at day 28, comparing two regimens. METHODS: A prospective, open, randomized clinical trial was conducted at a tertiary hospital in Barcelona, Spain. Individuals attending the emergency room because of potential sexual exposure to HIV were randomized to tenofovir disoproxil/emtricitabine (245/200 mg) plus either ritonavir-boosted lopinavir (400/100 mg) or raltegravir (400 mg). The primary endpoint was PEP non-completion at day 28. Secondary endpoints were adherence, adverse events and rate of seroconversions. This study was registered in ClinicalTrials.gov: NCT01576731. RESULTS: One-hundred-and-twenty-one individuals were randomized to receive ritonavir-boosted lopinavir and 122 to raltegravir (n = 243). PEP non-completion at day 28 was 43% with no significant difference between arms. We performed a modified ITT analysis including only those patients who attended on day 1 (n = 191). PEP non-completion in this subgroup was higher in the ritonavir-boosted lopinavir arm than in the raltegravir arm (34.6% versus 20.4%, P = 0.04), as was the number of patients lost to follow-up at day 28 (32.6% versus 21.6%, P = 0.08) and the proportion of patients with low adherence (49.2% versus 30.8%, P = 0.03). Adverse events were significantly more common in the ritonavir-boosted lopinavir arm (73.4% versus 60.2%, P = 0.007). There was an HIV seroconversion at day 90 in the raltegravir arm in a patient who had multiple potential sexual risk exposures before and after receiving PEP. CONCLUSIONS: Although we found no differences between arms regarding PEP non-completion, poor adherence and adverse events were significantly higher in patients allocated to tenofovir disoproxil/emtricitabine plus ritonavir-boosted lopinavir. These data support the use of raltegravir as the preferred third drug in current PEP recommendations.

A randomized clinical trial comparing ritonavir-boosted lopinavir versus maraviroc each with tenofovir plus emtricitabine for post-exposure prophylaxis for HIV infection.

OBJECTIVES: The objective of this study was to assess post-exposure prophylaxis (PEP) non-completion at day 28, comparing ritonavir-boosted lopinavir versus maraviroc, both with tenofovir disoproxil/emtricitabine as the backbone. METHODS: We conducted a prospective, open, randomized clinical trial. Individuals attending the emergency room because of potential sexual exposure to HIV and who met criteria for receiving PEP were randomized to one of two groups: tenofovir disoproxil/emtricitabine (245/200 mg) once daily plus either ritonavir-boosted lopinavir (400/100 mg) or maraviroc (300 mg) twice daily. Five follow-up visits were scheduled for days 1, 10, 28, 90 and 180. The primary endpoint was PEP non-completion at day 28. Secondary endpoints were adherence, adverse events and rate of seroconversions. This study was registered in ClinicalTrials.gov: NCT01533272. RESULTS: One-hundred-and-seventeen individuals were randomized to receive ritonavir-boosted lopinavir and 120 to maraviroc (n = 237). PEP non-completion at day 28 was 38% (n = 89), with significant differences between arms [ritonavir-boosted lopinavir 44% (n = 51) versus maraviroc 32% (n = 38), P = 0.05]. We performed a modified ITT analysis including only those patients who attended on day 1 (n = 182). PEP non-completion in this subgroup was also significantly higher in the ritonavir-boosted lopinavir arm (27% versus 13%, P = 0.004). The proportion of patients with low adherence was similar between arms (52% versus 47%, P = 0.56). Adverse events were reported by 111 patients and were significantly more common in the ritonavir-boosted lopinavir arm (72% versus 51%, P = 0.003). No seroconversions were observed during the study. CONCLUSIONS: PEP non-completion and adverse events were both significantly higher in patients allocated to ritonavir-boosted lopinavir. These data suggest that maraviroc is a well-tolerated antiretroviral that can be used in this setting.

Rate and predictors of non-AIDS events in a cohort of HIV-infected patients with a CD4 T cell count above 500 cells/mm³.

The reduction of risk of non-AIDS events after combined antiretroviral therapy (cART) initiation and the crude incidence rate (CIR) of these events in patients who control the viral load without cART (controllers) in a cohort of 574 antiretroviral-naive patients with a baseline CD4 T cell count above 500 cells/mm³ were assessed. Non-AIDS severe events were defined as a first admission to the hospital due to non-AIDS-defining malignancies, cardiovascular, neuropsychiatric, liver-related, or end-stage renal disease events. Potential determinants of non-AIDS/death events were studied using Cox regression models. Eighty-five non-AIDS/death events occurred during 6,062 persons-years of follow-up (PYFU) with a CIR of 1.4 per 100 PYFU. Factors associated with non-AIDS/death event were age (HR 3.4; 95% CI: 1.6-6.9), nadir CD4 below 350 cells/mm³ (HR 2.5; 95% CI: 1.4-4.6), and a last determination of viral load above the median (HR 1.9; 95% CI: 1.0-3.3). The CIR of non-AIDS/death events was 2.1 and 1.8 per 100 PYFU before and after cART in patients who started cART (n=446). A reduction of CIR of non-AIDS events after cART initiation was observed only in patients with a nadir of CD4 above 350 cells/mm³ (2.5 vs. 0.6 per 100 PYFU, p=0.004, and remained stable after cART in patients with a median nadir of CD4 below 350 cells/mm³. CIR was similar in elite, viremic, and noncontrollers (1.1, 1.0, and 1.5 per 100 PYFU, respectively, p=0.25). Reduction of CIR of non-AIDS events after cART initiation depends on nadir CD4 T cell count. Most of the controllers patients had a CIR similar to noncontrollers. These data support the early initiation of cART in HIV-infected patients.